tbuckley/cabot-search huggingface dataset:
All roads lead to COPD… or not?
Authors: Alvar Agusti, Rosa Faner
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>M.J. Divo and co-workers have developed and validated a Simple, Low cost and easy to IMplement (SLIM) calculator of the risk of developing incident chronic airflow limitation in middle-aged, ever-smokers with normal spirometry</b> https://bit.ly/3sOqtaU
Endothelial to mesenchymal transition: a novel pathological feature of pulmonary fibrosis
Authors: Sukhwinder Singh Sohal
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Endothelial to mesenchymal transition (EndMT) is central to pathogenesis of pulmonary fibrosis and a novel therapeutic target. It is now time for "out of the box" thinking to understand this insidious disease.</b>https://bit.ly/43GeetA
Oxidation alters IL-33 function: new insights in the biology of different forms of IL-33 and their relevance for COPD
Authors: Pieter S. Hiemstra, Irene H. Heijink
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The alarmin cytokine IL-33 alters airway epithelial cell function. The study reported by Strickson <i>et al</i>. shows that oxidised IL-33 employs a novel mechanism to increase epithelial mucin production that is relevant for chronic inflammatory lung diseases.</b> https://bit.ly/3OCTJse
Reply: Transitioning endothelial cells contribute to pulmonary fibrosis
Authors: Xiuju Wu, Kristina I. Boström, Yucheng Yao
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Differentiation trajectory from ECs to EC-like myofibroblasts and myofibroblasts may pass through a mesenchymal stage. This trajectory exists in a quiescent state in healthy lungs and may be activated when pathological stimuli trigger pulmonary fibrosis.</b> https://bit.ly/3QWfgyS
A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide
Authors: Roberto Monastero, Daniele Magro, Marika Venezia, Calogera Pisano, Carmela Rita Balistreri
Journal: Ageing Research Reviews (2023)

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations.
Hypoxia-inducible factor 1α activates the NLRP3 inflammasome to regulate epithelial differentiation in chronic rhinosinusitis
Authors: Bing Zhong, Silu Sun, Kai Sen Tan, Hsiao Hui Ong, Jintao Du, Feng Liu, Yafeng Liu, Shixi Liu, Luo Ba, Jing Li, De Yun Wang, Jing Liu
Journal: Journal of Allergy and Clinical Immunology (2023)
The Effectiveness of Shared Decision-making for Diabetes Prevention: 24- and 36-Month Results From the Prediabetes Informed Decision and Education (PRIDE) Trial
Authors: O. Kenrik Duru, Carol M. Mangione, Norman Turk, Janet Chon, Jeffery Fu, Grace Cheng, Felicia Cheng, Amanda Moss, Dominick Frosch, Kia Skrine Jeffers, Yelba Castellon-Lopez, Chi-Hong Tseng, Richard Maranon, Keith C. Norris, Tannaz Moin
Journal: Diabetes Care (2023)

OBJECTIVE We conducted a cluster-randomized, shared decision-making (SDM) trial offering lifestyle change, metformin, or both options, to adults at risk for diabetes in a primary care network (n = 20 practices). RESEARCH DESIGN AND METHODS We used propensity score matching to identify control patients and used electronic health record data to compare weight loss at 24 and 36 months of follow-up and diabetes incidence at 36 months of follow-up. RESULTS In adjusted post hoc analyses, SDM participants (n = 489) maintained modestly greater 24-month weight loss of −3.1 lb and 36-month weight loss of −2.7 lb versus controls (n = 1,430, both comparisons P &amp;lt; 0.001). SDM participants who chose both lifestyle change and metformin sustained weight loss at 36 months of −4.1 lb (P &amp;lt; 0.001 vs. controls). We found no differences in incident diabetes (15% of SDM participants, 14% of control participants; P = 0.64). CONCLUSIONS This is one of the first studies to demonstrate weight loss maintenance up to 36 months after diabetes prevention SDM.
Cold snare defect protrusion and incomplete polyp resection after forced cold snare polypectomy: a prospective observational study
Authors: Jun Arimoto, Hideyuki Chiba, Keiji Yamada, Takanori Nishiguchi, Mikio Kobayashi, Naoya Okada, Takuma Suto, Toshihiro Niikura, Hiroki Kuwabara, Michiko Nakaoka, Tomonori Ida
Journal: Endoscopy (2023)

Abstract Background Cold snare defect protrusions (CSDPs) that occur after cold snare polypectomy (CSP) are considered indicators of incomplete polyp resection (IPR). We have sometimes experienced difficulty resecting polyps with snaring alone; in such cases, a forcible pull on the snare by the endoscopist is necessary. We call this procedure “forced CSP (FCSP).” However, no previous studies have evaluated this procedure. Methods This was a prospective observational study. From November 2020 to June 2021, the frequency, safety, and validity of FCSP were evaluated at our hospital. We distinguished CSP with snaring alone performed by the assistant as conventional CSP, and CSP requiring a forcible pull on the snare by the endoscopist as FCSP. Results Of 1315 polyps removed, 105 underwent FCSP (8%). The perforation rate was 0% in both groups. The rate of CSDP after the procedure was 96.2% (101/105) with FCSP and 6.4% (77/1210) with conventional CSP (P&lt;0.001). The rate of IPR was 12.5% (13/104) with FCSP and 6.2% (75/1208) with conventional CSP (P=0.02). Multivariable analysis identified polyps located in the cecum (risk ratio [RR], 1.13; 95%CI 1.050–1.179; P=0.003) and polyps ≥6mm in diameter (RR, 2.37; 95%CI 2.146–2.542; P&lt;0.001) as independent risk factors for FCSP. Conclusions FCSP was performed on 105 polyps (8%) in this study. FCSP may be associated with the occurrence of CSDP and IPR. Further studies are necessary to confirm our results.
Arcturus (XBB.1.16) COVID-19 subvariant emergence in Indonesia
Authors: Tungki Pratama Umar
Journal: The Lancet (2023)

The COVID-19 pandemic is still a problem for the global community. New subvariants, primarily descended from omicron (B.1.1.529) sublineages, are continuously emerging and making this scenario harder to control due to their immune evasion capacity.1
Extra data to confirm waning protection of omicron (B.1.1.529) natural immunity
Authors: Maria Elena Flacco, Cecilia Acuti Martellucci, Lamberto Manzoli
Journal: The Lancet (2023)

We read with interest the meta-analysis authored by the COVID-19 Forecasting Team.1COVID-19 Forecasting TeamPast SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis.Lancet. 2023; 401: 833-842Summary Full Text Full Text PDF PubMed Scopus (151) Google Scholar The authors report a high degree of protection (>80%) against re-infection and COVID-19 disease for ancestral, alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) variants, but a higher risk of re-infection and symptomatic disease from the omicron BA.1 variant than other variants. We have been reassured to learn that the findings of a previous meta-analysis on the topic have been substantiated.2Flacco ME Acuti Martellucci C Baccolini V et al.Risk of reinfection and disease after SARS-CoV-2 primary infection: meta-analysis.Eur J Clin Invest. 2022; 52e13845Crossref PubMed Scopus (48) Google Scholar Regarding the role of vaccination, the authors suggest that natural immunity confers a protection against re-infection and disease comparable with two doses of SARS-CoV-2 vaccines. However, the number and characteristics of the included studies, the estimates of effect extracted, and the groups being compared in each of the six analyses shown in the study's figure 4 have not been reported, making it complex to repeat or just interpret these meta-analyses. Therefore (as a common practice in meta-analyses) we kindly ask the authors to share the data extracted from each of the included studies. Given the implications of these findings for vaccination policies,3Flacco ME Acuti Martellucci C Baccolini V et al.COVID-19 vaccines reduce the risk of SARS-CoV-2 reinfection and hospitalization: meta-analysis.Front Med. 2022; 91023507Crossref Scopus (23) Google Scholar and the need for continued monitoring, the scientific community would certainly benefit from access to these data. We declare no competing interests. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysisProtection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings. Full-Text PDF Open Access
Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): an open, parallel-group, randomised controlled trial
Authors: Joanna Moncrieff, Nadia Crellin, Jacki Stansfeld, Ruth Cooper, Louise Marston, Nick Freemantle, Glyn Lewis, Rachael Hunter, Sonia Johnson, Thomas Barnes, Nicola Morant, Vanessa Pinfold, Ruth Smith, Lyn Kent, Katherine Darton, Maria Long, Mark Horowitz, Robert Horne, Victoria Vickerstaff, Mithilesh Jha, Stefan Priebe
Journal: The Lancet Psychiatry (2023)

Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse.
Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial
Authors: William H K Schilling, Podjanee Jittamala, James A Watson, Simon Boyd, Viravarn Luvira, Tanaya Siripoon, Thundon Ngamprasertchai, Elizabeth M Batty, Cintia Cruz, James J Callery, Shivani Singh, Manisaree Saroj, Varaporn Kruabkontho, Thatsanun Ngernseng, Nuttakan Tanglakmankhong, Jaruwan Tubprasert, Mohammad Yazid Abdad, Wanassanan Madmanee, Jindarat Kouhathong, Kanokon Suwannasin, Watcharee Pagornrat, Nattaporn Piaraksa, Pongtorn Hanboonkunupakarn, Borimas Hanboonkunupakarn, Kittiyod Poovorawan, Manus Potaporn, Attasit Srisubat, Bootsakorn Loharjun, Walter R J Taylor, Vasin Chotivanich, Kesinee Chotivanich, Mallika Imwong, Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas P J Day, Mauro M Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J White, Nicholas J White, William HK Schilling, Weerapong Phumratanaprapin, Viravarn Luvira, James J Callery, Nicholas PJ Day, Sasithon Pukrittayakamee, Simon Boyd, Cintia Cruz, Arjen M Dondorp, Walter RJ Taylor, James A Watson, Watcharapong Piyaphanee, Kittiyod Poovorawan, Thundon Ngamprasertchai, Tanaya Siripoon, Borimas Hanboonkunupakarn, Kesinee Chotivanich, Podjanee Jittamala, Mallika Imwong, Janjira Thaipadungpanit, Maneerat Ekkapongpisit, Varaporn Kruabkontho, Thatsanun Ngernseng, Jaruwan Tubprasert, Mohammad Yazid Abdad, Elizabeth M Batty, Shivani Singh, Vasin Chotivanich, Wiroj Ruksakul, Chunlanee Sangketchon, Pongtorn Hanboonkunupakarn, Sakol Sookprome, Mauro Teixeira, Pedro J Almeida, Renato S Aguiar, Franciele Santos, Elizabeth Ashley, Manivanh Vongsouvath, Koukeo Phommasone, Audrey Dubot-Pérès, Sisouphanh Vidhamaly, Ammala Chingsanoon, Sixiong Bisayher, Danoy Chommanam, Terry John Evans, Vayouly Vidhamaly, Latsaniphone Boutthasavong, Mayfong Mayxay, Manus Potaporn, Attasit Srisubat, Bootsakorn Loharjun
Journal: The Lancet Infectious Diseases (2023)

Molnupiravir and ritonavir-boosted nirmatrelvir are the two leading oral COVID-19 antiviral treatments, but their antiviral activities in patients have not been compared directly. The aim of this ongoing platform trial is to compare different antiviral treatments using the rate of viral clearance as the measure of antiviral effect.
Complete resection of a rectal post-endoscopic-resection residual tumor including four endoclips using underwater endoscopic mucosal resection
Authors: Kosei Hashimoto, Yoshikazu Hayashi, Takaaki Morikawa, Masahiro Okada, Takahito Takezawa, Atsushi Kihara, Hironori Yamamoto
Journal: Endoscopy (2023)

Endoscopic submucosal dissection (ESD) can facilitate complete removal of residual tumors even after a failed endoscopic resection and even when endoclips are left in place [1]. However, ESD requires advanced endoscopic skills, long procedure times, and expensive devices. Underwater endoscopic mucosal resection (UEMR) has recently emerged as a game-changing technique for endoscopic polyp resection. UEMR is usually simpler, cheaper, and more reliable than the conventional endoscopic resection techniques. Additionally, UEMR could even assist resection of stage T1b lesions [2] and residual/recurrent colorectal lesions [3]. We illustrate the use of the UEMR technique for the complete endoscopic resection of a residual rectal tumor, including four endoclips, after endoscopic mucosal resection (EMR).
Re: Atezolizumab Plus Cabozantinib Versus Cabozantinib Monotherapy for Patients with Renal Cell Carcinoma After Progression with Previous Immune Checkpoint Inhibitor Treatment (CONTACT-03): A Multicentre, Randomised, Open-label, Phase 3 Trial
Authors: Matteo Rosellini, Elisa Tassinari, Andrea Marchetti, Veronica Mollica, Francesco Massari
Journal: European Urology (2023)
DNA Methylation at <i>ABCG1</i> and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial
Authors: Xiang Li, Xiaojian Shao, Minghao Kou, Xuan Wang, Hao Ma, Elin Grundberg, Lydia A. Bazzano, Steven R. Smith, George A. Bray, Frank M. Sacks, Lu Qi
Journal: Diabetes Care (2023)

To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight loss interventions with long-term changes in adiposity and body fat distribution.
Changes in Restricting Symptoms after Critical Illness among Community-Living Older Adults
Authors: Snigdha Jain, Ling Han, Evelyne A. Gahbauer, Linda Leo-Summers, Shelli L. Feder, Lauren E. Ferrante, Thomas M. Gill
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Survivors of critical illness have multiple symptoms, but how restricting symptoms change after critical illness and whether these changes differ among vulnerable subgroups is unknown.
Recognizing and Managing the Burdens of <i>Chronic Breathlessness</i> Alongside the Burdens of Chronic Obstructive Pulmonary Disease
Authors: David C. Currow, Rajam Iyer, Joseph Clark, Sujeet K. Rajan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Recognising and Managing the Burdens of Chronic Breathlessness Alongside the Burdens of COPD." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies
Authors: Guido Lancman, Kian Parsa, Krzysztof Kotlarz, Lisa Avery, Alaina Lurie, Alex Lieberman-Cribbin, Hearn Jay Cho, Samir S. Parekh, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa J. Sanchez, Santiago Thibaud, Sundar Jagannath, Ajai Chari
Journal: Blood Cancer Discovery (2023)

Abstract BCMA-targeted bispecific antibodies (BiAb) are efficacious in relapsed/refractory multiple myeloma; however, serious infections have emerged as important toxicities. In this retrospective study, we characterized all infections and their risk factors, and evaluated the impact of infection prophylaxis in patients treated with BCMA-targeted BiAbs. Among 37 patients, 15 (41%) experienced a grade 3–5 infection, with two infection-related deaths during deep remissions. Most (84%) infections occurred during disease remissions. The cumulative probability of grade 3–5 infection increased over time with no plateau. Among responders (n = 26), profound hypogammaglobulinemia occurred in 100% and continued throughout the entire duration of treatment. During periods when patients were receiving intravenous immunoglobulin (IVIg), the rate of grade 3–5 infections was 90% lower than during observation (incidence rate ratio, 0.10; 95% confidence interval, 0.01–0.80; P = 0.0307). No other risk factors for infection were identified. This study demonstrates that profound hypogammaglobulinemia is universal with BCMA-targeted BiAbs, with intravenous immunoglobulin potentially abrogating most of the infection risk. Significance: To the best of our knowledge, this is the first study to comprehensively analyze risk factors and mitigation strategies to prevent infections in myeloma patients receiving anti-BCMA bispecific antibodies. Profound and prolonged hypogammaglobulinemia was universal among responders, while immunoglobulin replacement was associated with 90% lower rates of grade 3–5 infections. See related commentary by Garfall and Stadtmauer, p. 427 . This article is featured in Selected Articles from This Issue, p. 419
Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study
Authors: Hayoung Choi, Soorack Ryu, Holly R. Keir, Yan Hui Giam, Alison J. Dicker, Lidia Perea, Hollian Richardson, Jeffrey T. J. Huang, Erin Cant, Francesco Blasi, Jennifer Pollock, Michal Shteinberg, Simon Finch, Stefano Aliberti, Oriol Sibila, Amelia Shoemark, James D. Chalmers
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Although inflammation and infection are key disease drivers in bronchiectasis, few studies have integrated host inflammatory and microbiome data to guide precision medicine. Objectives: To identify clusters among patients with bronchiectasis on the basis of inflammatory markers and to assess the association between inflammatory endotypes, microbiome characteristics, and exacerbation risk. Methods: Patients with stable bronchiectasis were enrolled at three European centers, and cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Clusters were compared in terms of microbiome composition (16S ribosomal RNA sequencing) and exacerbation risk over a 12-month follow-up. Measurements and Main Results: A total of 199 patients were enrolled (109 [54.8%] female; median age, 69 yr). Four clusters of patients were defined according to their inflammatory profiles: cluster 1, milder neutrophilic inflammation; cluster 2, mixed-neutrophilic and type 2; cluster 3, most severe neutrophilic; and cluster 4, mixed-epithelial and type 2. Lower microbiome diversity was associated with more severe inflammatory clusters (P < 0.001), and β-diversity analysis demonstrated distinct microbiome profiles associated with each inflammatory cluster (P = 0.001). Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more enriched in clusters 2 and 3 than in clusters 1 and 4. Furthermore, patients in cluster 2 (rate ratio [RR], 1.49; 95% confidence interval [CI], 1.16–1.92) and cluster 3 (RR, 1.61; 95% CI, 1.12–2.32) were at higher risk of exacerbation over a 12-month follow-up compared with cluster 1, even after adjustment for prior exacerbation history. Conclusions: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.
Accounting for Competing Events When Evaluating Long-Term Outcomes in Survivors of Critical Illness
Authors: Federico Angriman, Bruno L. Ferreyro, Michael O. Harhay, Hannah Wunsch, Laura C. Rosella, Damon C. Scales
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

The clinical trajectory of survivors of critical illness after hospital discharge can be complex and highly unpredictable. Assessing long-term outcomes after critical illness can be challenging because of possible competing events, such as all-cause death during follow-up (which precludes the occurrence of an event of particular interest). In this perspective, we explore challenges and methodological implications of competing events during the assessment of long-term outcomes in survivors of critical illness. In the absence of competing events, researchers evaluating long-term outcomes commonly use the Kaplan-Meier method and the Cox proportional hazards model to analyze time-to-event (survival) data. However, traditional analytical and modeling techniques can yield biased estimates in the presence of competing events. We present different estimands of interest and the use of different analytical approaches, including changes to the outcome of interest, Fine and Gray regression models, cause-specific Cox proportional hazards models, and generalized methods (such as inverse probability weighting). Finally, we provide code and a simulated dataset to exemplify the application of the different analytical strategies in addition to overall reporting recommendations.
Treatment of evolving cancers will require dynamic decision support
Authors: M.A.R. Strobl, J. Gallaher, M. Robertson-Tessi, J. West, A.R.A. Anderson
Journal: Annals of Oncology (2023)

Cancer research has traditionally focused on developing new agents, but an underexplored question is that of the dose and frequency of existing drugs. Based on the modus operandi established in the early days of chemotherapies, most drugs are administered according to predetermined schedules that seek to deliver the maximum tolerated dose and are only adjusted for toxicity. However, we believe that the complex, evolving nature of cancer requires a more dynamic and personalized approach. Chronicling the milestones of the field, we show that the impact of schedule choice crucially depends on processes driving treatment response and failure. As such, cancer heterogeneity and evolution dictate that a one-size-fits-all solution is unlikely-instead, each patient should be mapped to the strategy that best matches their current disease characteristics and treatment objectives (i.e. their 'tumorscape'). To achieve this level of personalization, we need mathematical modeling. In this perspective, we propose a five-step 'Adaptive Dosing Adjusted for Personalized Tumorscapes (ADAPT)' paradigm to integrate data and understanding across scales and derive dynamic and personalized schedules. We conclude with promising examples of model-guided schedule personalization and a call to action to address key outstanding challenges surrounding data collection, model development, and integration.